Systemic Autoimmunity

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications & trials

Abstract

This year, the branch further advanced its focus on the role of aberrant neutrophils and neutrophil extracellular traps (NETs) in driving autoimmune responses and end-organ damage in systemic autoimmune and chronic inflammatory diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and hidradenitis suppurativa. Ongoing efforts have continued to explore how innate immune pathways modulate autoimmunity and how these responses are shaped by immunometabolic changes, including modulation of the itaconate pathway and mitochondrial dysfunction, as well as circadian rhythm changes. We also reported new findings on multiomic assessments in lupus patients that predict or associate with vascular dysfunction and vascular wall inflammation, combining transcriptomic and proteomic approaches. Our team is also continuing to characterize neutrophil heterogeneity in health and across inflammatory diseases using cutting-edge techniques such as single-cell RNA sequencing, bulk RNA-seq, and ATAC-seq. These tools are being applied to delineate cellular subsets driving pathogenesis and to explore how various internal and external factors —including infections, pollutants, and diet - influence neutrophil biology, with implications for a number of chronic diseases. In parallel, we continue to utilize advanced imaging and functional vascular assays to assess vascular abnormalities in lupus patients and are actively conducting investigator-initiated clinical trials and natural history protocols at the NIH Clinical Center aimed at understanding, improving and potentially preventing vascular function in SLE.